'Imprinted' gels hold promise for future medical devices

August 28, 2001

WEST LAFAYETTE, Ind. -- Scientists at Purdue University are creating a biological sensor for glucose in research that ultimately may help to design "intelligent drug delivery" devices that could be implanted in the body to administer medications such as insulin.

The researchers formed a mesh-like "biomimetic" gel containing glucose molecules and then used a slightly acidic chemical to remove the glucose, leaving behind spaces where the glucose used to be. If placed in a liquid such as blood, glucose in the liquid diffuses into the gel and binds to the empty spaces. The gel is said to be "imprinted" for glucose molecules. Similar materials might be used in future medical devices to sense the presence of glucose, perhaps signaling an action to release insulin or other medications for diabetics, said chemical engineering doctoral student Mark Byrne.

"I'd be the first one to say that we have a lot of work to do, but our findings so far are very encouraging," said Byrne, who will discuss the work Tuesday (8/28) during the American Chemical Society's national meeting, Sunday through Thursday (8/26-30), in Chicago. The student is working with Nicholas A. Peppas, Purdue's Showalter Distinguished Professor of Chemical and Biomedical Engineering, and Kinam Park, a professor of pharmaceutics and biomedical engineering.

"There is a lot of interest in glucose sensing for diabetes research," Byrne said. "And that has been the main focus of this work. However, we are also working on systems that bind other molecules that are important for the treatment of other conditions.

"It's a tremendous task to design something that will eventually work in the human body."

The approach attempts to mimic how some molecules attach to "binding sites" on other molecules, similar to the way in which a key fits into a lock. Such binding is critical to various biological processes. Each binding site, however, must possess the proper shape and other characteristics for it to bind to a specific molecule.

The biomimetic gel contains numerous binding sites for glucose.

"Essentially, we are trying to design what nature has done so well, and that's a difficult thing to do," Byrne said. "We are creating artificial binding sites."

Artificial sensing mechanisms might one day be incorporated into medical devices implanted inside the body. The sensing mechanism would be part of a meshwork containing medications inside numerous microscopic cavities. Sensing glucose in the blood would automatically trigger the meshwork to expand, opening pores and releasing insulin or a medication that would enable the body to more efficiently absorb insulin.

"Ultimately, it would be nice to design something of this sort that would provide therapy for type one diabetes," Byrne said. "It would automatically sense when the glucose level was high, and then it would release an appropriate level of insulin. Then, whenever the glucose level went down again, the polymer gel would intelligently stop the release of insulin."

About 700,000 Americans suffer from insulin-dependent diabetes, also known as type one diabetes. People who have insulin-dependent diabetes must take insulin, either by injecting themselves with a needle at least twice a day or by using a battery-operated "insulin pump." The pump is worn outside the body, on a belt or in a pocket, and delivers a steady supply of insulin through a tube that connects to a needle placed under the skin.

Because insulin-dependent diabetes usually afflicts young people, it used to be called juvenile diabetes. About 12,000 children in the United States are diagnosed with the disorder every year.

The gels might be incorporated into a drug-dispensing system that receives signals from the sensors and then commands the meshwork to expand, releasing insulin. Another possibility is that the sensors themselves might directly command the meshwork to expand.

"The system would be sensitive to what is in the blood, and then, depending on what it sensed in the blood, would administer the right amount of drug," Byrne said.

Such applications probably will be at least five years in the future, researchers said.

An important aspect of the Purdue research is that the scientists have been able to make the gel with a non-toxic solvent and in water, meaning it would be compatible with the human body.

The gel is created by ultraviolet light, which causes molecules surrounding the glucose to form the binding sites. Then, the glucose is removed with an acidic chemical, leaving the empty, synthetic binding sites.
The research is supported by the National Institutes of Health, and the work is being conducted under the auspices of the recently formed Program in Therapeutic and Diagnostic Devices, which is supported by the National Science Foundation and directed by Peppas. The program brings together engineers from a broad range of backgrounds and expertise and was formed to train researchers in the field of biomedical devices, including artificial organs, biomaterials, controlled release devices and tissue-engineered materials.

Writer: Emil Venere, 765-494-4709, venere@purdue.edu

Related Web sites:
Nicholas Peppas: http://ChE.www.ecn.purdue.edu/ChE/Fac_Staff/Fac.Staff/peppas/
American Chemical Society: http://www.acs.org/


Biomimetic Materials for Drug Targeting and Drug Delivery
M.E. Byrne and N.A. Peppas

Engineering the molecular design of biomaterials by controlling recognition and specificity is the first step in coordinating and duplicating complex biological and physiological processes. Design and synthesis of artificial molecular structures capable of specific molecular recognition of biological molecules is classified and fundamentally defined by the term biomimetic materials. Molecular imprinting and microimprinting techniques, which create stereo-specific, three-dimensional binding cavities based on a biological compound of interest, will produce these biomimetic materials for intelligent drug delivery, drug targeting and tissue engineering devices. Developments of particular interest to the field are expected to be wide and far-reaching, such as recognition of undesirable biologicals, nano-scale patterning and recognition of proteins, site-specific interaction with tissues, etc. We have been successful in synthesizing novel glucose-binding molecules based on non-covalent directed interactions formed via molecular imprinting techniques within aqueous media. Numerous polymer systems were identified; however, the synthesis scheme and biological oriented application limited the choices to a few systems. Of particular importance in our polymer design is the network morphology, which spatially varies in crosslinking density (microporous and macroporous regions). Emphasis has also been placed on fundamental studies regarding the specific recognition event needed to produce a spatially defined recognition site. By tailoring the polymer gel structure composition, effective recognition sites can be created in polymer gels.

Sources: Nicholas Peppas, 765-494-7944, peppas@ecn.purdue.edu Source Mark Byrne, 765-494-3331, mbyrne@ecn.purdue.edu

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